Tiludronate treatment improves structural changes and symptoms of osteoarthritis in the canine anterior cruciate ligament model 英文参考文献.docVIP
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Tiludronate treatment improves structural changes and symptoms of osteoarthritis in the canine anterior cruciate ligament model 英文参考文献
Moreauetal.ArthritisResearchTherapy2011,13:R98
/content/13/3/R98
RESEARCH ARTICLE
OpenAccess
Tiludronatetreatmentimprovesstructural
changesandsymptomsofosteoarthritisinthe
canineanteriorcruciateligamentmodel
MaximMoreau1,2,PascaleRialland1,Jean-PierrePelletier2,JohanneMartel-Pelletier2,DanielLajeunesse2,
ChristelleBoileau2,JudithCaron2,DianeFrank1,BertrandLussier1,JeromeREdelCastillo1,GuyBeauchamp1,
DominiqueGauvin1,2,ThierryBertaim3,DominiqueThibaud4andEricTroncy1,2*
Abstract
Introduction:Theaimofthisprospective,randomized,controlled,double-blindstudywastoevaluatetheeffects
oftiludronate(TLN),abisphosphonate,onstructural,biochemicalandmolecularchangesandfunctioninan
experimentaldogmodelofosteoarthritis(OA).
Methods:Baselinevalueswereestablishedtheweekprecedingsurgicaltransectionoftherightcranial/anterior
cruciateligament,witheightdogsservingasOAplacebocontrolsandeightothersreceivingfourTLNinjections
(2mg/kgsubcutaneously)attwo-weekintervalsstartingthedayofsurgeryforeightweeks.Atbaseline,Week4
andWeek8,thefunctionaloutcomewasevaluatedusingkineticgaitanalysis,telemeteredlocomotoractimetry
andvideo-automatedbehaviourcapture.Painimpairmentwasassessedusingacompositenumericalratingscale
(NRS),avisualanalogscale,andelectrodermalactivity(EDA).Atnecropsy(Week8),macroscopicand
histomorphologicalanalysesofsynovium,cartilageandsubchondralboneofthefemoralcondylesandtibial
plateauswereassessed.Immunohistochemistryofcartilage(matrixmetalloproteinase(MMP)-1,MMP-13,anda
disintegrinandmetalloproteinasedomainwiththrombospondinmotifs(ADAMTS5))andsubchondralbone
(cathepsinK)wasperformed.Synovialfluidwasanalyzedforinflammatory(PGE andnitrite/nitratelevels)
2
biomarkers.Statisticalanalyses(mixedandgeneralizedlinearmodels)wereperformedwithana-thresholdof0.05.
Results:AbetterfunctionaloutcomewasobservedinTLNdogsthanOAplacebocontrols.Hence,TLNdogshad
lowergaitdisability(P=0.04atWeek8)andNRSscore(P=0.03,groupeffect),anddemonstratedbehavioursof
painlessconditionwiththevideo-capture(P
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